PROJECT SUMMARY Sleep apnea is a respiratory disorder that causes chronic intermittent hypoxia throughout the sleep cycle. Neuroimaging studies indicate that the hippocampus is particularly vulnerable to injury in sleep apnea. In addition to the involvement of this brain structure with spatial and recognition memory, hippocampal activity is coupled to and exerts influence on peripheral chemoreflexes and respiratory patterns. Thus, along with its cognitive effects, the neurophysiological changes in the hippocampus may contribute to the development of cardiovascular disease, the increased risk for stroke that occur with untreated sleep apnea. As the duration of untreated sleep apnea persists, the severity of the condition increases, as does the risk of developing increasingly significant cognitive deficit. We hypothesize that chronic intermittent hypoxia caused by sleep apnea triggers reactive oxygen species signaling, resulting in duration-dependent changes to hippocampal neurophysiology and, in turn, causing progressive degradation in hippocampal-based cognition. We test this hypothesis in a rodent model of sleep apnea in which animals are exposed to different durations of chronic intermittent hypoxia. We examine the resulting effects on hippocampal neurophysiology and neurogenesis, focusing on principal neurons involved in learning and memory pathways. In addition to dissecting the role of reactive oxygen species signaling in cognitive changes, we explore the mechanistic origin of this signaling and the potential interaction between cardio-respiratory organs (i.e., carotid bodies) and the hippocampus. The mechanistic insights gained from this work will inform the development of more effective therapies to prevent, or fully reverse, cognitive decline in a condition that affects the quality of life for many Americans.